In the past year we have initiated collaboration with epidemiologists at the NCI to study the interaction between molecular and classical risk factors of oral cancer. We are using biological samples already collected in a case-control study of oral and pharyngeal cancer conducted in Puerto Rico. The study focused on Puerto Rico because of the especially high incidence of oral cancer known to occur there. Our analyses thus far have focused on applying highly sensitive techniques for detection of human papilloma virus using polymerase chain reaction methods. We extracted DNA from 150 paraffin embedded sections of tumor tissue. Preliminary results indicate that this virus is infrequently present in these oral cancers from Puerto Rico. We have also characterized a polymorphism at the aryl hydrocarbon receptor, a key mediator of the detoxification pathways involving P450 cytochrome. Statistical analyses suggest that this molecular variant may interact with exposure to risk factors such as smoking and drinking in influencing risk of oral cancer. We have been developing plans and protocols for performing molecular analyses of several additional DNA polymorphisms that have been shown to be associated with risk of other forms of cancer.